Genetic Variant TRPA1:p.Asn128Asn (chr8-72069083-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_007332.3(TRPA1):c.384C>T(p.Asn128Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,846 control chromosomes in the GnomAD database, including 15,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2452 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12624 hom. )

Consequence

TRPA1
NM_007332.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.28

Publications

11 publications found

Variant links:

Genes affected

TRPA1 (HGNC:497): (transient receptor potential cation channel subfamily A member 1) The structure of the protein encoded by this gene is highly related to both the protein ankyrin and transmembrane proteins. The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control. [provided by RefSeq, Jul 2008]

TRPA1 links:

MSC-AS1 (HGNC:48724): (MSC antisense RNA 1)

MSC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 8-72069083-G-A is Benign according to our data. Variant chr8-72069083-G-A is described in ClinVar as Benign. ClinVar VariationId is 3058871.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPA1	NM_007332.3 link	c.384C>T	p.Asn128Asn	synonymous_variant	Exon 3 of 27	ENST00000262209.5	NP_015628.2	O75762
TRPA1	XM_011517624.3 link	c.459C>T	p.Asn153Asn	synonymous_variant	Exon 4 of 28		XP_011515926.1
TRPA1	XM_011517625.3 link	c.384C>T	p.Asn128Asn	synonymous_variant	Exon 5 of 29		XP_011515927.1	O75762

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPA1	ENST00000262209.5 link	c.384C>T	p.Asn128Asn	synonymous_variant	Exon 3 of 27	1	NM_007332.3	ENSP00000262209.4		O75762

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24537

AN:

152028

Hom.:

2445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0893

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.156

GnomAD2 exomes

AF:

0.138

AC:

34765

AN:

251478

AF XY:

0.139

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.0693

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.123

AC:

179123

AN:

1461700

Hom.:

12624

Cov.:

AF XY:

0.124

AC XY:

90052

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.278

AC:

9314

AN:

33476

American (AMR)

AF:

0.0706

AC:

3159

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

3548

AN:

26136

East Asian (EAS)

AF:

0.312

AC:

12369

AN:

39700

South Asian (SAS)

AF:

0.181

AC:

15610

AN:

86254

European-Finnish (FIN)

AF:

0.112

AC:

6002

AN:

53420

Middle Eastern (MID)

AF:

0.129

AC:

742

AN:

5766

European-Non Finnish (NFE)

AF:

0.108

AC:

120545

AN:

1111834

Other (OTH)

AF:

0.130

AC:

7834

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

8895

17791

26686

35582

44477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4692

9384

14076

18768

23460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.161

AC:

24558

AN:

152146

Hom.:

2452

Cov.:

AF XY:

0.161

AC XY:

11938

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.276

AC:

11429

AN:

41470

American (AMR)

AF:

0.0891

AC:

1363

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

489

AN:

3470

East Asian (EAS)

AF:

0.286

AC:

1482

AN:

5178

South Asian (SAS)

AF:

0.179

AC:

864

AN:

4814

European-Finnish (FIN)

AF:

0.109

AC:

1159

AN:

10596

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7333

AN:

67996

Other (OTH)

AF:

0.157

AC:

332

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1009

2019

3028

4038

5047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.131

Hom.:

797

Bravo

AF:

0.163

Asia WGS

AF:

0.192

AC:

668

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.108

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TRPA1-related disorder

Benign:1

Nov 19, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.6

(source)

DANN

Benign

0.66

PhyloP100

2.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over